These experiments have two goals: First, to test the hypothesis that the organization of cerebral neocortex is malleable in adult mammals and second to test the idea that cortical reorganization is regulated by certain widespread cortical inputs. The rat motor cortex (MI) has been chosen as a model for these studies because it is possible to assess changes both in sensory representation and in motor output in this system, and it is also possible to relate MI reorganization to modification in the cortical control of movement. Specifically, the proposed experiments will identify the types of adaptive responses that occur in rat MI following a peripheral injury (forelimb amputation). MI reorganization will be evaluated first with intracortical microstimulation and somatic sensory receptive field mapping techniques. The extent of reorganization will be compared in neonatally or adult-amputated rats to identify the potential limits of reorganization in this system. Preliminary data suggest that MI reorganization occurs with early postnatal amputation. Next, the location and extent of reorganization will be further tested by using axonal tracers to examine connectional changes induced by forelimb amputation. Finally, topographic reorganization will be studied after noradrenergic (NA) or cholinergic (ACh) inputs to MI are eliminated. These experiments should help to localize sites of reorganization and should further clarify the role of these widespread inputs in regulating cortical organization. These experiments will provide important new information concerning the flexibility of the relationship between the cortex and the somatic periphery, and the results may suggest strategies for enhancing or suppressing cortical responses to peripheral injury.